Controlled release dosage forms have received a great deal of attention for their use as drug delivery systems. These systems are capable of delivering a drug at a predetermined rate such that drug concentrations can be maintained at therapeutically effective levels over an extended period, with the potential for minimizing side effects.
Various approaches exist for the preparation of controlled release dosage forms. One commonly known technique is to form a matrix by entrapping the drug in excipients (i.e., cellulose ether derivatives). Diffusion and/or erosion operate to release the active substance, depending on the properties of the drug and the polymer incorporated in the formulation. This approach generally results in non-zero order release kinetics, T. Higuchi, J. Pharm. Sci., 52:1145 (1965). The amount of drug available at the absorption site therefore decreases with time, which is the major drawback of these dosage forms. In zero order release, the amount of drug release remains constant with respect to time. Prior methods for preparing zero order controlled release dosage forms include those operating by a rate-controlling membrane, G. Kallstrant, B. Ekman, J. Pharm. Sci., 72:772 (1983), and by osmotic pumps, F. Theeuwes, J. Pharm. Sci., 64:1987 (1975) and T. Higuchi, U.S. Pat. No. 4,439,196 (1984).
Dosage forms for controlled release applications containing cellulose ether derivatives are known. However, none of these prior formulations provides a zero order release form as described and claimed in this application.
U.S. Pat. No. 4,389,393 claims controlled release dosage forms made from a carrier base material comprising one or more hydroxypropyl methylcellulose (HPMC) or a mixture of one or more HPMC and up to 30% other cellulose ethers, where the carrier base comprises 25.8% or less of the total tablet weight.
U.S. Pat. No. 4,540,566 discloses the technology utilizing anionic surfactants to prolong drug release from a dosage form containing a low viscosity grade of HPMC.
U.S. Pat. No. 4,556,678 claims a controlled release propranolol formulation that utilizes HPMC and hydroxypropyl cellulose (HPC).
European Patent 109,320 relates to a theophylline composition that contains 18-35% HPMC, 7.5-22.5% of another hydrophilic binder and 0.5-1% of an internal hydrophobic lubricant.
European Patent 111,144 discloses a hydrophilic matrix tablet having one or more sustained release layers with differing drug concentrations using HPMC. The patent describes a hydrophilic matrix system using a gradient layer to achieve a zero order controlled release, this system applicable only for water soluble drugs.